A histone H3 lysine 27 demethylase regulates animal posterior development.

摘要: The recent discovery of a large number histone demethylases suggests central role for these enzymes in regulating methylation dynamics. Histone H3K27 trimethylation (H3K27me3) has been linked to polycomb-group-protein-mediated suppression Hox genes and animal body patterning, X-chromosome inactivation possibly maintenance embryonic stem cell (ESC) identity. An imbalance owing overexpression the methylase EZH2 implicated metastatic prostate aggressive breast cancers. Here we show that JmjC-domain-containing related proteins UTX JMJD3 catalyse demethylation H3K27me3/2. is enriched around transcription start sites many HOX primary human fibroblasts, which are differentially expressed, but selectively excluded from loci ESCs, largely silent. Consistently, RNA interference inhibition led increased H3K27me3 levels at some gene promoters. Importantly, morpholino oligonucleotide zebrafish homologue resulted mis-regulation hox striking posterior developmental defect, was partially rescued by wild-type, not catalytically inactive, UTX. Taken together, findings identify small family with important, evolutionarily conserved roles regulation anterior-posterior development.